1. Field of the Invention
This invention concerns novel isoquinoline derivatives and therapeutically acceptable addition salts thereof useful as cardiotonics.
2. Description of the Prior Art
Digitalis pharmaceuticals such as digoxin or digitoxin have been used as cardiotonics for the therapy of heart failure.
Cardiotonic activity has also been reported for nicotinonitrile derivatives (for instance, referred to Japanese patent laid-open No. Sho 57-70868), imidazolone derivatives (for instance, referred to Japanese patent laid-open No. Sho 59-155368) and dihydropyridadine derivatives (for instance, referred to Japanese patent laid-open No. Sho 58-74679).
As an isoquinoline derivative having cardiotonic activity, a compound represented by the general formula (I) described in the present specification, wherein R.sub.1 represents methyl group and R.sub.2 represents cyano or acetyl group has already been filed as Japanese patent application No. Sho 61-623.
Digitalis pharmaceuticals used at present for therapy require highly skilled techniques for use since their safety range is narrow and they provide a problem of causing undesirable side activity such as irregular pulses.
Further, nicotinonitrile derivatives, imidazolone derivatives, dihydropyridadinone derivatives, etc., which have already been reported also involve problems such as low cardiotonic activity, narrow safety range, increase in the number of myocardiac movement or high animal toxicity.
The present inventors have continued an earnest study with an aim of obtaining a compound having a broad safety range and with no side activity and, as a result, have accomplished this invention based on the findings that isoquinoline derivatives have high cardiotonic activity and less toxicity.